Innovations In Clinical Neuroscience

2015 Abstracts of Poster Presentations

A peer-reviewed, evidence-based journal for clinicians in the field of neuroscience

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[ V O L U M E 1 2 , N U M B E R 1 1 – 1 2 , N O V E M B E R – D E C E M B E R 2 0 1 5 , S U P P L E M E N T C ] Innovations in CLINICAL NEUROSCIENCE 5 successfully treated for acute episodes. This standard design, used in the pivotal trials for all treatments that have gained regulatory approval f or prevention of relapse, requires discontinuing a treatment and usually defines relapse based on specific threshold scores on selected rating scales for mania or depression (HAM-D, MADRS, and YMRS). This study design, however, has important limitations and the results may not generalize or be relevant to the real- world clinical patient population who might benefit from maintenance treatment. Methods: We present a novel clinical trial design with TAK-375SL as an add-on treatment to prolong remission in bipolar disorder bipolar I subjects who are stable on their current treatment (either singly or a combination of lithium valproate, lamotrigine, any antidepressant, aripiprazole, olanzapine, quetiapine risperidone, and ziprasidone. TAK- 375SL is a sublingual formulation of ramelteon, a melatonin receptor agonist approved for the treatment of insomnia. It is postulated that melatonin receptor agonistic properties may help maintain mood stability and prolong remission periods in patients with bipolar disorder. In this Phase III, randomized, double-blind, placebo- controlled study, the safety and efficacy of 0.1mg, 0.4mg and 0.8mg of TAK-375SL were evaluated for maintenance treatment of bipolar I disorder. Results: The study screened 1,247 subjects of which 642 were randomized to placebo (164) or TAK-375SL 0.1mg (164), 0.4mg (160), or 0.8mg (154). Baseline demographics were similar across all groups. Low rates of relapse were seen across all treatment groups and there was no statistical difference seen in the number of relapses across the groups, placebo, (n=37; 23.6%), Tak375-SL 0.1mg (n=29; 17.9%), 0.4mg (n=28; 18.2%) and 0.8mg (n=35; 23.5%). A total of 38 subjects reported SAEs: placebo (19) and TAK-375SL 0.1mg (15), 0.4mg (6), and 0.8mg (8); 358 TEAEs were seen in 120 subjects in the placebo group, 319 in 103 subjects in the 0.1mg, 259 in 106 subjects in the 0 .4mg, and 295 in 105 subjects in the 0.8mg group respectively. Conclusion: A Phase III registration study designed with input from the FDA is described. In this study TAK-375SL was not efficacious in prevention of relapse in stable patients with bipolar I disorder. TAK- 375SL was safe and well-tolerated. Cognitive function in vortioxetine clinical trials in major depressive disorder: a meta-analysis Presenters: 1 McIntyre RS, 2 Harrison J, 3 Loft H, 4 Jacobson W, 3 Olsen CK Affiliations: 1 University Health Network, University of Toronto; 2 Metis Cognition Ltd. & Alzheimer Center, VU University Medical Center; 3 H. Lundbeck A/S; 4 Takeda Development Center Americas Background: Patients with major depressive disorder (MDD) often exhibit deficits in cognitive function. This meta-analysis investigated the effect of vortioxetine on cognitive function in patients with MDD. Objective: To find the effect of vortioxetine on cognitive function in patients with MDD. Methods: The efficacy of vortioxetine in the treatment of cognitive dysfunction in MDD was evaluated in three eight-week, placebo-controlled studies (NCT01422213, NCT01564862, NCT00811252), two of which included duloxetine as an active reference for assay sensitivity. The Digit Symbol Substitution Test (DSST) assessed cognitive function and the Montgomery-Åsberg Depression Rating Scale (MADRS) assessed depressive symptom severity. To evaluate the independent effect of treatment on cognition, we adjusted for the effect of depressive symptoms assessed by MADRS. Standardized effect sizes (SES) were used. Results: DSST changes from baseline at Week 8 (SES based on number of correct symbols) versus placebo (FAS, ANCOVA, LOCF), without adjusting for change in MADRS total score, were vortioxetine 10/20mg: 0.254 (p<0.05, n=175), d uloxetine: 0.176 (NS, n=187) (NCT01564862); vortioxetine 10mg: 0.477 (p<0.001, n=193), vortioxetine 20mg: 0.482 (p<0.001, n=204) (NCT01422213); vortioxetine 5mg: 0.265 (p<0.05, n=152), duloxetine 0.073 (NS, n=144) (NCT00811252). After adjustment for MADRS, vortioxetine separated from placebo (p<0.0001), SES=0.24 in the meta- analysis of all three studies. For the two studies with duloxetine, vortioxetine separated from placebo (p<0.05), SES=0.19, whereas duloxetine did not separate from placebo (p=0.6171), SES=0.04. The difference between vortioxetine and duloxetine was statistically significantly (p<0.05) in favor of vortioxetine, SES=0.16. Conclusion: In patients with MDD, vortioxetine statistically significantly improved the performance on the DSST compared to placebo in the meta-analyses, both with and without adjusting for the MADRS. Disclosures: RS McIntyre is a consultant to and receives speaker fees from Takeda, Lundbeck, AstraZeneca, Eli-Lilly, Janssen, Otsuka, Sunovion, Allergan, and Pfizer. J Harrison has received honoraria and paid consultancy from Lundbeck A/S and the Takeda Pharmaceutical Company, Ltd. H Loft and CK Olsen are employees of H. Lundbeck A/S. W Jacobson is an employee of the Takeda Pharmaceutical Company, Ltd. Funding by: H. Lundbeck A/S and Takeda Pharmaceutical Company, Ltd. Efficacy and safety of ITI-007 in clinical studies of schizophrenia Presenters: Vanover K, Davis R, O'Gorman C, Saillard J, Weingart M, Mates S Affiliations: Intra-Cellular Therapies, Inc. (ITI) Background: Schizophrenia is a serious mental illness that exerts a

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